The Disorders Induced by Iodine Deficiency

This paper reviews present knowledge on the etiology, pathophysiology, complications, prevention, and therapy of the disorders induced by iodine deficiency. The recommended dietary allowances of iodine are 100 μg/day for adults and adolescents, 60–100 μg/day for children aged 1 to 10 years, and 35–40 μg/day in infants aged less than 1 year. When the physiological requirements of iodine are not met in a given population, a series of functional and developmental abnormalities occur including thyroid function abnormalities and, when iodine deficiency is severe, endemic goiter and cretinism, endemic mental retardation, decreased fertility rate, increased perinatal death, and infant mortality. These complications, which constitute a hindrance to the development of the affected populations, are grouped under the general heading of iodine deficiency disorders (IDD). At least one billion people are at risk of IDD. Iodine deficiency, therefore, constitutes one of the most common preventable causes of mental deficiency in the world today. Most of the affected populations live in montainous areas in preindustrialized countries, but 50 to 100 million people are still at risk in Europe. The most important target groups to the effects of iodine deficiency from a public health point of view are pregnant mothers, fetuses, neonates, and young infants because the main complication of IDD, i.e., brain damage resulting in irreversible mental retardation, is the consequence of thyroid failure occurring during pregnancy, fetal, and early postnatal life. The main cause of endemic goiter and cretinism is an insufficient dietary supply of iodine. The additional role of naturally occurring goitrogens has been documented in the case of certain foods (milk, cassava, millet, nuts) and bacterial and chemical water polluants. The mechanism by which the thyroid gland adapts to an insufficient iodine supply is to increase the trapping of iodide as well as the subsequent steps of the intrathyroidal metabolism of iodine leading to preferential synthesis and secretion of triiodotyronine (T3). They are triggered and maintained by increased secretion of TSH, which is ultimately responsible for the development of goiter. The acceleration of the main steps of iodine kinetics and the degree of hyperstimulation by TSH are much more marked in the pediatric age groups, including neonates, than in adults, and the development of goiter appears as an unfavorable side effect in the process of adaptation to iodine deficiency during growth. The most serious complication of iodine deficiency is endemic cretinism, a syndrome characterized by irreversible mental retardation together with either a predominant neurological syndrome or predominant hypothyroidism, or a combination of both syndromes. The prophylactic action of iodine on the incidence of both types of cretinism demonstrates the fundamental etiological role of iodine deficiency. The possible additional roles of thyroid growth-blocking immunoglobulins and of selenium deficiency have been suggested. The pathogenic roles of maternal and fetal hypothyroidism or a combination of both as well as of hypothyroidism present during the postnatal period are clearly established, but the relative importance of the three mechanisms in the pathogenesis of the various clinical manifestations of endemic cretinism is not entirely clearly established. A particularly important issue established both in severe and moderate conditions of iodine deficiency is that obvious neurointellectual deficits due to the deficiency are also frequently observed in individuals who do not present any of the other signs of endemic cretinism. The status of iodine nutrition was recently reevaluated in all European countries, including those in the Eastern part of the continent. Iodine deficiency is presently under control in only 5 countries (Austria, Finland, Norway, Sweden, and Switzerland). All other countries are still affected to varying degrees, especially in the southern and central parts of the continent. The public health consequences of iodine deficiency in Europe are an elevated thyroidal uptake of radioiodine that aggravates the risk of thyroid cancer in case of a nuclear accident, the occasional presence of neurointellectual deficits in schoolchildren, elevated frequencies of transient primary hypothyroidism and of transient hyperthyrotropinemia in young infants. Neonatal screening for congenital hypothyroidism using serum TSH as primary screening test appears as a particularly sensitive index of the effects of iodine deficiency at a population level and as a monitoring tool in the evaluation of the effects of iodine prophylaxis. Although theoretically entirely preventable, IDD still prevail in the world because of various socioeconomical, cultural, and political limitations to adequate programs of iodine supplementation, especially in Europe. Prevention of iodine deficiency in Western countries is most efficiently achieved by programs of salt iodization at the level of one part of iodide to 10,000–50,000 parts salt, depending on the degree of the deficiency and on salt intake. Iodized salt should be made available not only for household salt but also in industrial food production including cheese and bread as well as for animal consumption. As a matter of fact, milk appears as the main source of iodine in many industrialized countries. In preindustrialized countries where food fortification with iodine is impossible to organize, prophylaxis and therapy of IDD can be achieved extremely efficiently by the administration of large quantities of iodine (20-960 mg) in the form of slowly resorbable iodized oil administered by intramuscular injections or orally. This approach not only corrected thyroid function on a long-term basis with progressive disappearance of goiter but also prevented the occurrence of endemic cretinism and endemic mental retardation.